Phase II Multicentered Study of Exemestane and Lapatinib in Advanced Hormone-responsive Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 3
- 主要终点
- recommended dose of lapatinib given in combination with standard dose of exemestane in patients with advanced hormone-responsive breast cancer
研究概览
简要总结
Aromatase inhibitors are the standard treatment for hormone responsive advanced breast cancer. The combination of the aromatase inhibitor exemestane with with another breast cancer drug that blocks epidermal growth factor receptor (EGFR) and Erb-2 activity (lapatinib) is being studied for the possibility of improving response to therapy, and delaying resistance to endocrine therapy.
详细描述
The recommended dose of lapatinib will be determined in the first part of the study. In the second part of the study, patients will receive the recommended dose of lapatinib and exemestane daily, taken orally.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of breast cancer
- •Indication for hormonal therapy (ER and/or PgR positive)
- •Stage IV disease
- •Female gender
- •Postmenopausal status (patients treated with LHRH analogs are eligible for the Phase II part of the study)
- •At least one target or non-target lesion according to RECIST criteria
- •ECOG Performance Status 0-2
- •Adequate bone marrow (neutrophils > or = 1.500/mm³, platelets > or = 100.000/mm³ and hemoglobin > or = 9 g/dl), hepatic (GOT, GPT < 2.5 e bilirubin <1.25 times the value of upper normal limit) and renal (creatinine < 1.25 times the value of upper normal limit) function
- •Adequate cardiac function (FEVS > or = 50%)
- •Able to take oral medications
- •Life expectancy > 3 months
- •Signed informed consent
排除标准
- •Any previous hormone therapy for metastatic disease
- •More than one line of chemotherapy for metastatic disease (first line chemotherapy is permitted)
- •Symptomatic cerebral metastases
- •Planned concomitant radiation therapy in the first month of therapy (for those patients participating in the dose finding phase of the study)
- •Previous therapy with exemestane, including as adjuvant therapy (previous therapy with non-steroidal aromatase inhibitors is permitted)
- •Previous or concurrent malignancy in past 5 years (excluding adequately treated basal cel or spinocellular skin cancer and in situ carcinoma of the cervix)
- •Treatment with experimental pharmacologic therapy within 4 weeks of enrollment in the study
- •Unable or unwilling to provide signed informed consent
- •Any concurrent illness that would, in the Investigator's opinion, contraindicate the use of the study drugs.
- •Active infection
- •Assumption of CYP3A4 inhibitors or inducers (ketoconazole, itraconazole, fluconazole, macrolide antibiotics, antidepressives, calcium-antagonists, cimetidine, carbamazepine, phenytoin, barbiturates, rifampicin e glucocorticoids)
- •Pregnancy or lactation
- •Unable to comply with follow-up
- •Active hepatobiliary disease (with the exception of Gilbert's syndrome, asymptomatic biliary calculi, hepatic metastases or stabile chronic hepatopathy)
研究组 & 干预措施
A
phase II
干预措施: exemestane (Drug)
A
phase II
干预措施: lapatinib (Drug)
结局指标
主要结局
recommended dose of lapatinib given in combination with standard dose of exemestane in patients with advanced hormone-responsive breast cancer
时间窗: one month after dose selection for each of 3 possible dose levels
proportion of patients free from progression
时间窗: at 6 months
次要结局
- objective response(at 3 and 6 months)
- time to progression(at 12 months)
- overall survival(18 months)
- Treatment related toxicity(every 4 weeks)
- prognostic role of molecular markers and circulating tumor cells(at 18 months)